tbuckley/cabot-search huggingface dataset:
Diagnostic yield and clinical relevance of expanded genetic testing for cancer patients
Authors: Ozge Ceyhan-Birsoy, Gowtham Jayakumaran, Yelena Kemel, Maksym Misyura, Umut Aypar, Sowmya Jairam, Ciyu Yang, Yirong Li, Nikita Mehta, Anna Maio, Angela Arnold, Erin Salo-Mullen, Margaret Sheehan, Aijazuddin Syed, Michael Walsh, Maria Carlo, Mark Robson, Kenneth Offit, Marc Ladanyi, Jorge S. Reis-Filho, Zsofia K. Stadler, Liying Zhang, Alicia Latham, Ahmet Zehir, Diana Mandelker
Journal: Genome Medicine (2022)

Genetic testing (GT) for hereditary cancer predisposition is traditionally performed on selected genes based on established guidelines for each cancer type. Recently, expanded GT (eGT) using large hereditary cancer gene panels uncovered hereditary predisposition in a greater proportion of patients than previously anticipated. We sought to define the diagnostic yield of eGT and its clinical relevance in a broad cancer patient population over a 5-year period.
The Expression of Hypoxia-Inducible Factor 1α Is a Favorable Independent Prognostic Factor in Renal Cell Carcinoma
Authors: Anders Lidgren, Ylva Hedberg, Kjell Grankvist, Torgny Rasmuson, Janos Vasko, Börje Ljungberg
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Renal cell carcinoma (RCC) is the most common malignancy of the kidney composed of specific tumor types. The sporadic conventional RCCs are, in contrast to the other RCC types, characterized by a high rate of von Hippel-Lindau (VHL) mutations and hypermethylation. The majority of these tumors lack functional VHL protein (pVHL) that leads to increased hypoxia-inducible factor 1α (HIF-1α) expression. The pVHL is the physiologic regulator of the activity of HIF-1α by targeting it to the proteasome for degradation under normoxia. Both pVHL and HIF-1α target other genes that are important for cancer survival and proliferation. Expression of HIF-1α has been linked to poor prognosis in different malignancies, although few studies have been done on the relation between HIF-1α and clinical variables in RCC. Experimental Design: HIF-1α protein expression was analyzed in tumor tissue from 92 patients with RCC. HIF-1α was quantified by Western blot relative to a positive control. Results: The HIF-1α protein was expressed as two bands which strongly correlated (r = 0.906, P &amp;lt; 0.001); therefore, they were added and the sum evaluated against clinicopathologic variables. There was no association between HIF-1α and gender, stage, grade, tumor size, or vein invasion. Conventional RCCs had significantly higher HIF-1α expression compared with papillary and chromophobe RCCs and kidney cortex. In conventional RCC, HIF-1α was an independent prognostic factor. Conclusion: HIF-1α levels varied significantly between the different RCC types. In conventional RCC, HIF-1α was an independent prognostic factor. These data indicate that HIF-1α is involved in tumorogenesis and progression of RCC. Evaluation of other HIF target gene products and correlation to angiogenesis seems warranted.
Skiascopy and its Practical Application to the Study of Refraction.
Journal: JAMA (1895)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Covid-19: UK will not buy Evusheld owing to “insufficient data” on protection, government says
Authors: Elisabeth Mahase
Journal: BMJ (2022)

The UK government has said that it will not procure the covid-19 drug Evusheld-a combination of two long acting antibodies, tixagevimab and cilgavimab-because of "insufficient data" on the duration of protection it provides against omicron and its subvariants.
American Public Health Association.
Journal: JAMA (1884)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Neuregulin 4 suppresses NASH-HCC development by restraining tumor-prone liver microenvironment
Authors: Peng Zhang, Zhimin Chen, Henry Kuang, Tongyu Liu, Jiaqiang Zhu, Linkang Zhou, Qiuyu Wang, Xuelian Xiong, Ziyi Meng, Xiaoxue Qiu, Ramiah Jacks, Lu Liu, Siming Li, Carey N. Lumeng, Qing Li, Xiang Zhou, Jiandie D. Lin
Journal: Cell Metabolism (2022)
Systematic single-variant and gene-based association testing of thousands of phenotypes in 394,841 UK Biobank exomes
Authors: Konrad J. Karczewski, Matthew Solomonson, Katherine R. Chao, Julia K. Goodrich, Grace Tiao, Wenhan Lu, Bridget M. Riley-Gillis, Ellen A. Tsai, Hye In Kim, Xiuwen Zheng, Fedik Rahimov, Sahar Esmaeeli, A. Jason Grundstad, Mark Reppell, Jeff Waring, Howard Jacob, David Sexton, Paola G. Bronson, Xing Chen, Xinli Hu, Jacqueline I. Goldstein, Daniel King, Christopher Vittal, Timothy Poterba, Duncan S. Palmer, Claire Churchhouse, Daniel P. Howrigan, Wei Zhou, Nicholas A. Watts, Kevin Nguyen, Huy Nguyen, Cara Mason, Christopher Farnham, Charlotte Tolonen, Laura D. Gauthier, Namrata Gupta, Daniel G. MacArthur, Heidi L. Rehm, Cotton Seed, Anthony A. Philippakis, Mark J. Daly, J. Wade Davis, Heiko Runz, Melissa R. Miller, Benjamin M. Neale
Journal: Cell Genomics (2022)
Association Between Standardized Mortality Ratio and Utilization of Care in US Veterans With Drug-Resistant Epilepsy Compared With All US Veterans and the US General Population
Authors: Zulfi Haneef, Rizwana Rehman, Aatif M. Husain
Journal: JAMA Neurology (2022)

<h3>Importance</h3> Drug-resistant epilepsy (DRE) is thought to be associated with increased mortality, but larger population-based studies are lacking. Additionally, the benefit of effective management in DRE lacks evidence. <h3>Objective</h3> To examine the association of utilization of care with mortality in US veterans with DRE. <h3>Design, Setting, and Participants</h3> Observational cohort study conducted between October 1, 2013, and March 31, 2020. Mortality statistics in US veterans with DRE were compared to the US general population and all veterans within the Veterans Health Administration. Epilepsy was defined as use of 1 or more antiseizure medications (ASMs) for 30 days or longer with a seizure diagnosis or 1 inpatient or 2 outpatient encounters with an epilepsy diagnosis. DRE was defined as the use of 2 or more ASMs. Among 9.6 million US veterans, 164 435 (1.7%) had epilepsy, of whom 55 571 (33.8%) had DRE. Epilepsy and DRE were administratively identified based on criteria noted in design. Identified participants were included for analysis. <h3>Exposures</h3> Veterans with DRE. <h3>Main Outcomes and Measures</h3> Standardized mortality ratio (SMR). <h3>Results</h3> Among US veterans with DRE, the mean (SD) age was 58.3 (15.4) years, and 49 430 individuals (88.9%) were male. Of ethnicity data gathered, 3170 individuals (5.7%) were Hispanic or Latino, 50 599 (91.1%) were not Hispanic or Latino, 842 (1.5%) declined to answer, and 960 (1.7%) were recorded as unknown. Of race data gathered, 516 individuals (0.9%) were American Indian or Alaskan Native, 270 (0.5%) were Asian, 11 316 (20.4%) were Black or African American, 587 (1.1%) were of multiple races, 453 (0.8%) were Native Hawaiian or Pacific Islander, 39 543 (71.2%) were White, 1697 (3.1%) declined to answer, and 1189 (2.1%) were recorded as unknown. SMR was 1.50 (95% CI, 1.47-1.53) compared with the US general population and 1.56 (95% CI, 1.53-1.59) compared with all veterans. Utilization rates were 81.1% (n = 45 057) for neurology clinic evaluation, 66.4% (n = 36 905) for magnetic resonance imaging (MRI), and 49.6% (n = 27 546) for electroencephalography (EEG) testing. Only 8350 individuals (15.0%) had comprehensive epilepsy evaluations and 3357 (6.0%) had epilepsy monitoring. Multivariable analysis revealed an association between lower mortality and neurology clinic evaluation, EEG, MRI, epilepsy monitoring, and the use of more than 2 ASMs after adjusting for age and comorbidities. <h3>Conclusions and Relevance</h3> Mortality rates were significantly higher in US veterans with DRE compared to the general population. Better utilization of comprehensive epilepsy care, diagnostic services, and medications were each associated with reduced mortality. These findings indicate that appropriate management of DRE is critical in this population.
Study Quality Must Be Considered When Evaluating Long-term Outcomes of Antenatal Corticosteroid Therapy in Children—Reply
Authors: Kiran Ninan, Kellie E. Murphy, Sarah D. McDonald
Journal: JAMA Pediatrics (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Adult-Onset Genetic Central Nervous System Disorders Masquerading as Acquired Neuroinflammatory Disorders
Authors: Xavier Ayrignac, Clarisse Carra-Dallière, Cecilia Marelli, Guillaume Taïeb, Pierre Labauge
Journal: JAMA Neurology (2022)

Adult-onset genetic disorders may present with clinical and magnetic resonance imaging (MRI) features suggestive of acquired inflammatory diseases. An ever-growing number of potentially treatable adult-onset genetic neuroinflammatory disorders have been described in the past few years that need to be rapidly identified.Adult-onset acquired neuroinflammatory disorders encompass a large group of central nervous system (CNS) diseases with varying presentation, MRI characteristics, and course, among which the most common is multiple sclerosis. Despite recent progress, including the discovery of specific autoantibodies, a significant number of adult-onset neuroinflammatory disorders with progressive or relapsing course still remain without a definite diagnosis. In addition, some patients with genetic disorders such as leukodystrophies, hemophagocytic lymphohistiocytosis, or genetic vasculopathies can mimic acquired neuroinflammatory disorders. These genetic disorders, initially described in pediatric populations, are increasingly detected in adulthood thanks to recent progress in molecular genetics and the larger availability of high-throughput sequencing technologies.Genetic adult-onset neuroinflammatory diseases are at the border between primary CNS inflammatory diseases and systemic disorders with multiorgan involvement and predominantly neurologic manifestations. Neurologists must be aware of the main clues and red flags so they can confirm a diagnosis early, when some of these genetic disorders can be successfully treated.
Framework for Clinical Trials in Cerebral Small Vessel Disease (FINESSE)
Authors: Hugh S. Markus, Wiesje M. van Der Flier, Eric E. Smith, Philip Bath, Geert Jan Biessels, Emily Briceno, Amy Brodtman, Hugues Chabriat, Christopher Chen, Frank-Erik de Leeuw, Marco Egle, Aravind Ganesh, Marios K. Georgakis, Rebecca F. Gottesman, Sun Kwon, Lenore Launer, Vincent Mok, John O’Brien, Lois Ottenhoff, Sarah Pendlebury, Edo Richard, Perminder Sachdev, Reinhold Schmidt, Melanie Springer, Stefan Tiedt, Joanna M. Wardlaw, Ana Verdelho, Alastair Webb, David Werring, Marco Duering, Deborah Levine, Martin Dichgans
Journal: JAMA Neurology (2022)

Cerebral small vessel disease (SVD) causes a quarter of strokes and is the most common pathology underlying vascular cognitive impairment and dementia. An important step to developing new treatments is better trial methodology. Disease mechanisms in SVD differ from other stroke etiologies; therefore, treatments need to be evaluated in cohorts in which SVD has been well characterized. Furthermore, SVD itself can be caused by a number of different pathologies, the most common of which are arteriosclerosis and cerebral amyloid angiopathy. To date, there have been few sufficiently powered high-quality randomized clinical trials in SVD, and inconsistent trial methodology has made interpretation of some findings difficult.
Achieving Diagnostic Equity in Cardiovascular Disease
Authors: Urmimala Sarkar, Kirsten Bibbins-Domingo
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Executive Summary: International Clinical Practice Guidelines for Pediatric Ventilator Liberation, A PALISI Network Document
Authors: Samer Abu-Sultaneh, Narayan Prabhu Iyer, Analía Fernández, Michael Gaies, Sebastián González-Dambrauskas, Justin Christian Hotz, Martin C.J. Kneyber, Yolanda M López-Fernández, Alexandre T. Rotta, David K Werho, Arun Kumar Baranwal, Bronagh Blackwood, Hannah J Craven, Martha A. Q. Curley, Sandrine Essouri, Jose Roberto Fioretto, Silvia MM Hartmann, Philippe Jouvet, Steven Kwasi Korang, Gerrard F Rafferty, Padmanabhan Ramnarayan, Louise Rose, Lyvonne N Tume, Elizabeth C Whipple, Judith Ju Ming Wong, Guillaume Emeriaud, Christopher W Mastropietro, Natalie Napolitano, Christopher J.L. Newth, Robinder G Khemani
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Rationale: Pediatric specific ventilator liberation guidelines are lacking despite the many studies exploring elements of extubation readiness testing. The lack of clinical practice guidelines has led to significant and unnecessary variation in methods used to assess pediatric patients’ readiness for extubation. Methods: Twenty-six international experts comprised a multi-professional panel to establish pediatric specific ventilator liberation clinical practice guidelines, focusing on acutely hospitalized children receiving invasive mechanical ventilation for more than 24 hours. Eleven key questions were identified and first prioritized using the Modified Convergence of Opinion on Recommendations and Evidence. Systematic review was conducted for questions which did not meet an a-priori threshold of ≥80% agreement, with Grading of Recommendations, Assessment, Development, and Evaluation methodologies applied to develop the guidelines. The panel evaluated the evidence, drafted, and voted on the recommendations. Measurements and Main Results: Three questions related to systematic screening, using an extubation readiness testing bundle and use of a spontaneous breathing trial as part of the bundle met Modified Convergence of Opinion on Recommendations criteria of ≥80% agreement. For the remaining 8 questions, 5 systematic reviews yielded 12 recommendations related to the methods and duration of spontaneous breathing trials; measures of respiratory muscle strength; assessment of risk of post-extubation upper airway obstruction and its prevention; use of post-extubation non-invasive respiratory support; and sedation. Most recommendations were conditional and based on low to very low certainty of evidence. Conclusion: This clinical practice guideline provides a conceptual framework with evidence-based recommendations for best practices related to pediatric ventilator liberation. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Association of Maternal Antipsychotic Prescription During Pregnancy With Standardized Test Scores of Schoolchildren in Denmark
Authors: Xiaoqin Liu, Betina Bitsch Trabjerg, Trine Munk-Olsen, Jakob Christensen, Julie Werenberg Dreier
Journal: JAMA Internal Medicine (2022)

An increasing number of individuals fill antipsychotic prescriptions during pregnancy, and concerns have been raised about prenatal antipsychotic exposure on neurodevelopmental outcomes.To examine whether maternal prescription fill for antipsychotics during pregnancy was associated with performance in standardized tests among schoolchildren.This register-based cohort study included 667 517 children born in Denmark from January 1, 1997, to December 31, 2009, and who were attending public primary and lower secondary school. All children had completed at least 1 language (Danish) or mathematics test as part of the Danish National School Test Program between 2010 and 2018. Data were analyzed from November 1, 2021, to March 31, 2022.Antipsychotic prescriptions filled by pregnant individuals were obtained from the Danish National Prescription Register.Differences in standardized test scores (range, 1-100; higher scores indicate better test results) in language and mathematics between children of mothers with and without antipsychotic prescription fills during pregnancy were estimated using linear regression models. Seven sensitivity analyses, including a sibling-controlled analysis, were performed.Of the 667 517 children included (51.2% males), 1442 (0.2%) children were born to mothers filling an antipsychotic prescription during pregnancy. The mean (SD) age of children at the time of testing spanned from 8.9 (0.4) years in grade 2 to 14.9 (0.4) years in grade 8. Maternal prescription fill for antipsychotics was not associated with performance in language (crude mean test score: 50.0 [95% CI, 49.1-50.9] for the exposed children vs 55.4 [95% CI, 55.4-55.5] for the unexposed children; adjusted difference, 0.5 [95% CI, -0.8 to 1.7]) or in mathematics (crude mean test score: 48.1 [95% CI, 47.0-49.3] for the exposed children vs 56.1 [95% CI, 56.1-56.2] for the unexposed children; adjusted difference, 0.4 [95% CI, -1.0 to 1.8]). There was no evidence that results were modified by the timing of filling prescriptions, classes (first-generation and second-generation) of antipsychotics, or the most commonly prescribed antipsychotic monotherapies, including chlorprotixene, flupentixol, olanzapine, zuclopenthixol, quetiapine, perphenazine, and methotrimeprazine. The results remained robust across sensitivity analyses, including sibling-controlled analyses, negative control exposures analyses, and probabilistic bias analyses.In this register-based cohort study, maternal prescription fill for antipsychotics during pregnancy did not appear to be associated with standardized test scores in the offspring. The findings provide further reassuring data on offspring neurodevelopmental outcomes associated with antipsychotic treatment during pregnancy.
BindVAE: Dirichlet variational autoencoders for de novo motif discovery from accessible chromatin
Authors: Meghana Kshirsagar, Han Yuan, Juan Lavista Ferres, Christina Leslie
Journal: Genome biology (2022)

We present a novel unsupervised deep learning approach called BindVAE, based on Dirichlet variational autoencoders, for jointly decoding multiple TF binding signals from open chromatin regions. BindVAE can disentangle an input DNA sequence into distinct latent factors that encode cell-type specific in vivo binding signals for individual TFs, composite patterns for TFs involved in cooperative binding, and genomic context surrounding the binding sites. On the task of retrieving the motifs of expressed TFs in a given cell type, BindVAE is competitive with existing motif discovery approaches.
Modeling liver hereditary hemorrhagic telangiectasia with right heart overload to the core of liver sinusoidal endothelial cells
Authors: Orlando Musso
Journal: Hepatology (2022)

1 INSERM, INRAE Univ RennesNutrition Metabolism and CancerRennesFrance *Correspondence Orlando Musso, INSERM, INRAE, Univ Rennes, Nutrition Metabolism and Cancer, Rennes, France. Email: [email protected]
A wearable electrochemical biosensor for the monitoring of metabolites and nutrients
Authors: Minqiang Wang, Yiran Yang, Jihong Min, Yu Song, Jiaobing Tu, Daniel Mukasa, Cui Ye, Changhao Xu, Nicole Heflin, Jeannine S. McCune, Tzung K. Hsiai, Zhaoping Li, Wei Gao
Journal: Nature Biomedical Engineering (2022)